TABLE 1

Definition of exacerbation as reported by studies included in the meta-analysis

Study [ref.], yearDefinition of exacerbation
Zheng et al. [1], 2014“At least a 2 day persistence of two (type II moderate) or all three (type III, severe) major symptoms (worsening dyspnoea, increase in sputum purulence or volume), or of any one major symptom plus at least one minor symptom (type I, mild) (upper airway infection, unexplained fever, and increased wheezing)”
Tse et al. [20], 2013“Two of the following three symptoms: increase in shortness of breath, volume, or purulence of sputum”
Schermer et al. [26], 2009“An episode with one or more subsequent unscheduled contacts with either a general practitioner or a chest physician due to worsening of respiratory symptoms”
Bachh et al. [27], 2007“Increased dyspnea and/or cough associated with a change in quality and quantity of sputum, which led the patient to seek medical attention and lasting for >3 days”
Decramer et al. [3], 2005“Increase in dyspnoea, cough, or both associated with a change in quality and quantity of sputum, which led the patient to seek medical attention and which lasted for at least 3 days”
Gerrits et al. [29], 2003“Re-hospitalisation for chronic obstructive pulmonary disease”
Pela et al. [24], 1999“The worsening of the clinical profile of the patient with increased cough, dyspnea and expectoration with mucopurulent sputum, with or without fever requiring medical intervention. If the total score of the following questionnaire amounted to >3 points, the occurrence of an exacerbation was confirmed: fever: absent=0, present=1; cough: mild=0, moderate=1, severe=2; mucus: unchanged=0, increased=1, increased and purulent=2; dyspnoea: unchanged=0, increased=1, severely increased=2”
Hansen et al. [19], 1994“A mucopurulent sputum with new or worse cough, plus one or more of the following: new general malaise; new symptoms of cold; fever (38°C or above); increased dyspnoea; increased mucus production; increased viscosity of sputum; new onset of foul-tasting sputum; increased difficulty of expectoration; increase in erythrocyte sedimentation rate in relation to exacerbation; leucocytosis in relation to exacerbation; and/or pneumonia confirmed by X-ray”
Rasmussen and Glennow [25], 1988; Boman et al. [23], 1983“Mucopurulent or purulent sputum and cough (new or aggravated) plus one or more of the following symptoms: general malaise; new symptoms of common cold; fever (>38°C); breathlessness; increased mucus production; increased sputum-thickness; foul tasting sputum; increased difficulty of expectoration; increase in erythrocyte sedimentation rate; leucocytosis or pneumonia”
McGavin et al. [22], 1985“New or deteriorating cough with increased sputum purulence lasting for at least 48 hours plus at least one of the following: general malaise, any recorded fever greater than 38°C, increased breathlessness, increased sputum volume or thickness, increased difficulty in expectoration”
Babolini et al. [21], 1980“A discrete change in the course of the disease marked by rapid increase in coughing and sputum output and purulence, associated with worsening of chest physical signs and possibly dyspnoea but not necessarily with fever”
Grassi and Morandini [28], 1976“Episode or sudden aggravation of the typical signs and symptoms”